JC23 (Medicine) - Cerebellar Lesions and Gait Disorders Flashcards

Question

Tics * Describe * Types * Control?

Answer 1

abrupt **stereotyped repetitive movements** involving discrete muscle groups □ Can mimic normal coordinated movements, vary in intensity and lack rhythm → **Motor tics**, eg. eye-blinks, shoulder shrugs, facial grimaces… → **Phonic tics**, eg. barks, grunts, swearing… □ May be temporarily **inhibited by will power** and usually **disappear by sleep**

Answer 2

no underlying structural lesions, usually onset in childhood and resolves after 20y → Transient tic disorder: last \<1y, occurs in normal children → Gilles de la Tourette syndrome: otherwise unexplained motor + phonic tics with onset \<21y

Answer 3

tics begin abruptly, are persistent or are problematic → Eg. dopaminergic drugs, stimulants, neuroleptics, other inherited diseases

Answer 4

**Behavioural Tx (eg. habit reversal treatment) as mainstay** Drugs: □ **D2 blockers**: haloperidol, pimozole, aripiprazole → risk of tardive dyskinesia → ↓use nowadays □ **Dopamine depleters**: tetrabenazine → usually 1st choice nowadays after failure of behavioural Tx □ **α-agonists**: guanfacine, clonidine → used if concomitant ADHD + Tourette syndrome

Answer 5

brief, **repetitive**, involuntary sudden **‘shock-like’ jerks** of muscle groups Results from focal discharge from **cortex** (majority), subcortical or spinal cords

Answer 6

□ **Physiological**: hypnic (during sleep transitions), anxiety-related, exercise-related □ **Essential myoclonus** □ **Epileptic myoclonus**: a/w seizure syndrome, eg. juvenile myoclonic epilepsy □ Symptomatic (secondary) myoclonus: → Focal **CNS lesions**, eg. post-stroke, CNS tumour → Metabolic and toxic **encephalopathies** → **Neurodegenerative** diseases, eg. CJD, Alzheimer’s disease, CBD → Metabolic **storage diseases** → **Progressive myoclonic epilepsy** (with progressive cognitive decline, seizures, ataxia and death)

Answer 7

**Sustained/intermittent involuntary muscle contractions** in antagonistic muscle groups causing **abnormal movements or distorted postures** Dystonic movements are typically patterned, twisting and may be tremulous, i.e. dystonic tremor

Answer 8

□ **Focal**: a group of muscles, eg. blepharospasm, oromandibular dystonia, cervical dystonia □ **Segmental**: contiguous groups of muscles, eg. craniobrachial dystonia, Meige syndrome □ **Multifocal**: ≥2 non-contiguous groups of muscles □ **Generalized**, eg. idiopathic torsion dystonia

Answer 9

Exacerbating factors: voluntary action, fatigue, stress and emotional states Relieving factors: sensory tricks (geste antagoniste, eg. touching face), sleep and relaxation Extent of limb involvement: LL onset in early onset vs facial, neck or UL onset in late onset

Answer 10

**Idiopathic** torsion dystonia: → **Hereditary:** early onset (\<21y), LL focal onset becoming generalized → **Sporadic**: adult onset (\>21y), UL, facial or cervical onset w/o generalization **Secondary** dystonia → **Brain injury**, eg. cerebral palsy, head injury → **Neurodegenerative diseases**, eg. Parkinsonism, spinocerebellar ataxia, Huntington’s disease → **Drug-induced**, eg. anticonvulsants, CCB, DA-agonist, levodopa, neuroleptics

Answer 11

Pharmacotherapy: **levodopa** (if young-onset), **anticholinergic**/BZD (if adult-onset) **Botox** injection

Answer 12

Anatomical: Anterior lobe, Posterior lobe, Flocculonodular lobe Functional: * Vestibulocerebellum - flocculonodular lobe for **vestibular reflexes** * Spinocerebellum - Vermis and intermediate zone for **error-detection** of truncal and distal muscles * Cerebrocerebellum - hemisphere for **motor planning, rapidly alternating movement**

Answer 13

Spinocerebellum - Vermis and intermediate zone for **error-detection** of truncal and distal muscles □ **Nystagmus**: horizontal or vertical nystagmus □ Truncal **ataxia**: wide-based cerebellar gait, Romberg –ve □ LL **dysmetria**: heel-shin test

Answer 14

Cerebrocerebellum - hemisphere for **motor planning, rapidly alternating movement** abnormalities in limb coordination □ Limb **ataxia**: UL dysmetria, intention tremor, dysdiadochokinesia, rebound, gait ataxia □ Scanning **dysarthria**: same emphasis put on each syllable

Answer 15

**Vascular**  Cerebellar ischaemia  Cerebellar haemorrhage **Drugs and toxins\***  Antiepileptics, eg. phenytoin  Chemo, eg. cytarabine, 5FU  Alcohol **Infectious**  Meningoencephalitis  ADEM

Answer 16

**Autoimmune**\*  Multiple sclerosis  Miller-Fisher syndrome  SLE, Behcet’s, coeliac… **Paraneoplastic** degeneration\*  SCLC, gyne, breast, lymphoma **Neoplastic**, esp CPA tumours **Metabolic**\*  Chronic alcoholism  Wernicke encephalopathy (vitamin B1 deficiency)  Vitamin E deficiency  Hypothyroidism

Answer 17

Congenital  Chiari malformation  Dandy-Walker syndrome  Cerebellar agenesis Hereditary\*  Spinocerebellar ataxia (AD) - SCA  Friedreich’s ataxia (AR) - FA  Ataxia-telangiectasia (AR) - AT  Wilson’s disease (AR)  Mitochondrial diseases Neurodegenerative\*  Multiple system atrophy (MSA)  Progressive supranuclear palsy (PSP)  Cerebellar degeneration

Answer 18

idiopathic **degeneration of substantia nigra** with intraneuronal **Lewy bodies**

Answer 19

Extrapyramidal symptoms: 1. **Tremor**: develops early unilaterally, 4-6Hz, decrease in late stage due to bradykinesia and rigidity 2. **Rigidity**: _‘Cogwheel’ or ‘lead-pipe’_ rigidity, flexed/stooped posture 3. **Akinesia or bradykinesia**: slowness, hesitance, motor arrest 4. **Postural instability**: imbalance and falls, propulsion/ retropulsion when standing

Answer 20

Loss of finger dexterity Shuffling gait Masked face Monotonous speech Drooling saliva (slow swallowing)

Answer 21

**Idiopathic Parkinsonism** (Parkinson’s disease, PD): commonest, 80% of cases **Parkinsonian-plus syndromes**: □ Multisystem atrophy (**MSA**) □ Progressive supranuclear palsy (**PSP**, Steele-Richardson-Olzewski syndrome) □ Corticobasal degeneration (**CBD**) **Secondary (symptomatic) parkinsonism**: □ **Post-encephalitic**, eg. encephalitis lethargica □ **Drug-induced**, eg. **dopamine-depleting/anti-dopaminergic drugs,** lithium, antihistamines □ Chronic head trauma, eg. **‘punch-drunk’ syndrome** □ **Neoplastic**, eg. parasagittal meningioma **Inherited neurodegenerative** diseases: □ **Wilson’s disease** □ Hallervorden-Spatz syndrome **Pseudoparkinsonism:** □ Cerebral arteriosclerotic disease Essential tremor, Cerebellar tremor (intention), Akinetic Huntington's chorea

Answer 22

□ Motor symptoms: Depletion of dopaminergic neurons, **degeneration of nigrostriatal pathway** → ↓dopamine input to striatum → balance shifted towards indirect pathway → **bradykinesia, rigidity** □ **Cognitive** symptoms: degeneration of **mesocortical/mesolimbic dopaminergic pathways** □ **Autonomic dysfunction**: dopamine depletion in **hypothalamus** □ **Dementia**: degeneration of **cholinergic nucleus** (spread of Lewy Bodies to cortex)

Answer 23

**Neuropsychiatric**: * Depression * Anxiety * PD-psychosis: common in late stages, can be due to levodopa PD-**Dementia** **Autonomic** dysfunction: * Postural hypotension * Constipation * Sweating Miscellaneous: fatigue, pain, sleep disturbance, sexual disturbance, anosmia

Answer 24

Presentation: * Young onset with **strong family history** * **Rapid progression** * **Early instability** and falls * Early and prominent **dementia** Extent: * Pyramidal/ **cerebellar signs** * **Autonomic** dysfunction Treatment: * **Poor response to Levodopa**

Answer 25

UKPD Society Brain Bank Clinical Diagnostic Criteria **Clinical features**: ***_Bradykinesia_*** + at least one of: * Muscular ***_rigidity_***, * 4-6Hz rest ***_tremor_***, * ***_postural instability_*** without primary visual, vestibular, cerebellar or proprioceptive_dysfunction **Exclusion criteria:** exclude other diseases **Supportive prospective positive criteria:** 3+ for def. dx **Unilateral onset** **Rest tremor present** Progressive, persistent **asymmetrical involvement** excellent response to **levodopa for 5 years** or more Severe levodopa induced chorea clinical course of **ten years** or more

Answer 26

□ Onset/course: sudden onset, rapid progression, young onset with strong FHx of other ds □ Clinical pattern: early and prominent dementia, early frequent falls, early incontinence, no tremor in presence of significant bradykinesia □ S/S of other causes: pyramidal/cerebellar signs/autonomic dysfx (MSA), gaze palsy (PSP), cortical signs/alien hand syndrome (CBD) □ Retrospective: poor treatment response to levodopa (PD usually excellent response)

Answer 27

**CT/MRI** to rule out alternative causes **Dopaminergic SPECT/PET**: ↓dopamine activity in basal ganglia: examples: * DaT scan (SPECT) * 18F-Dopa Scan, 11C- Raclopride PET scan * MRI - DTI, DWI, ADC mapping

Answer 28

Initial treatment: **Levodopa** **Adjunctive treatment** for **dyskinesia or motor fluctuation** Options: **dopamine agonist, MAO-B inhibitor, COMT inhibitor** **Surgical Tx** considered for pharmacologically refractory cases

Answer 29

eg. **Sinemet** (levodopa + carbidopa), **Madopar** (levodopa + beserazide)

Answer 30

MoA: Levodopa is precursor of dopamine → decarboxylated into dopamine → replenishes inadequate dopamine in striatum Carbidopa/ Beserazide: Peripheral DOPA decarboxylase inhibitor cannot pass BBB → Decrease peripheral decoration of levodopa → Decrease peripheral side effects, Increase central availability

Answer 31

**→ Nausea, vomiting, orthostatic hypotension** **→ Confusion and visual hallucinations** **→ Impulse control disorders:** eg. compulsive cleaning, gambling, hypersexuality → Dopamine **dysregulation syndrome/ Addiction**: compulsive use of dopaminergic drug (addiction)

Answer 32

1. **Loss of efficacy** 2. **Motor fluctuations:** unpredictable response to levodopa with **On and Off episodes** 3. **Dyskinesia**: Chorea and dystonia in peak-dose or diphasic 4. **Psychiatric** complications

Answer 33

**Dopamine agonist (DA),** eg. rotigotine (skin patch), pramipexole, ropinirole, apomorphine **MAO-B inhibitor (MAOI),** eg. selegiline, rasagiline □ MoA: inhibitor of monoamine oxidase → decrease DA breakdown **Catechol-O-methyltransferase (COMT) inhibitor,** eg. entacapone □ MoA: ↓methylation of dopamine and levodopa → increase duration of action of levodopa

Answer 34

**Amantadine**: □ MoA: unknown, likely a/w NMDA receptor blockade □ Use: treatment of LD-induced dyskinesias **Anticholinergics,** eg. orphenidrine, benzhexol (Artane), benztropine □ MoA: inhibitor muscarinic cholinergic fibres in striatum → ↓inhibition □ Use: initial therapy in young-onset pt w/ prominent dystonia and tremor

Answer 35

**Destructive neurosurgery:** → **Thalamotomy** for control of medically intractable tremor → **Pallidotomy** for control of LD-induced dyskinesias, rigidity, bradykinesia, tremor **Deep brain stimulation (DBS):** medically refractory tremor or motor fluctuation

Answer 36

**Psychosis**: **antipsychotics** (eg. quetiapine, clozapine, pimavanserin) PD-**Dementia: cholinesterase inhibitor** **Depression**: **desipramine** (TCA) and citalopram (Refute most SSRIs) (SSRIs can interact with MAOI (5HT syndrome) and a/w risk of ↑motor symptoms)

JC23 (Medicine) - Cerebellar Lesions and Gait Disorders Flashcards

(62 cards)